A5069346041- interferon and immune responses
- NF-κB Signaling Pathways
- Genomics and Chromatin Dynamics
- Immune Response and Inflammation
- RNA Research and Splicing
- RNA modifications and cancer
- RNA regulation and disease
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- Lipid Membrane Structure and Behavior
- Cholesterol and Lipid Metabolism
- Chromatin Remodeling and Cancer
- Immune cells in cancer
University of California, Los Angeles
2020-2025
Human BioMolecular Research Institute
2024
Laboratory of Molecular Genetics
2024
A group of autoinflammatory disorders termed relopathies arise as a consequence NF-κB dysregulation. Genetic loss the subunit RelB in humans and mice leads to autoimmunity lethal multi-organ inflammatory pathology. Our recent study showed that this pathology is independent type I interferon signaling, further identified dysregulation set pro-inflammatory target genes. However, it remains unknown how these motif-containing Here, we report epigenome profiling studies revealing associated with...
Inducible nucleosome remodeling at hundreds of latent enhancers and several promoters shapes the transcriptional response to Toll-like receptor 4 (TLR4) signaling in macrophages. We aimed define identities transcription factors that promote TLR-induced remodeling. An analysis strategy based on ATAC-seq single-cell enriched for genomic regions most likely undergo revealed factor nuclear κB (NF-κB) bound all high-confidence peaks marking during primary TLR4 ligand, lipid A. Deletion NF-κB...
Development of embryonic stem cells (ESCs) into neurons requires intricate regulation transcription, splicing, and translation, but how these processes interconnect is not understood. We found that polypyrimidine tract binding protein 1 (PTBP1) controls splicing DPF2, a subunit BRG1/BRM-associated factor (BAF) chromatin remodeling complexes. Dpf2 exon 7 inhibited by PTBP1 to produce the DPF2-S isoform early in development. During neuronal differentiation, loss allows inclusion DPF2-L...
Adaptive immunity and the five vertebrate NF-κB family members first emerged in cartilaginous fish, suggesting that divergence helped to facilitate adaptive immunity. One specialized function of Rel protein macrophages is activation Il12b, which encodes a key regulator T cell development. We found Il12b exhibits much greater dependence than inducible innate genes macrophages, with unique dimers depending on heightened intrinsic DNA-binding affinity. Chromatin immunoprecipitation followed by...
The five NF-κB family members and three nuclear IκB proteins play important biological roles, but the mechanisms by which distinct of these protein families contribute to selective gene transcription remain poorly understood, especially at a genome-wide scale. Using nascent transcript RNA-seq, we observed considerable overlap between p50-dependent IκBζ-dependent genes in Toll-like receptor 4 (TLR4)-activated macrophages. Key immunoregulatory genes, including Il6 , Il1b Nos2 Lcn2, Batf, are...
SUMMARY The five NF-κB family members and three nuclear IκB proteins play important biological roles, but the mechanisms by which distinct contribute to selective gene transcription remain poorly understood, especially at a genome-scale level. Using nascent transcript RNA-seq, we observed considerable overlap between p50-dependent IκBζ-dependent genes in Toll-like receptor 4 (TLR4)-activated macrophages. Key immunoregulatory genes, including Il6 , Il1b Nos2 Lcn2, Batf, are among p50-IκBζ...
Abstract An understanding of the mechanisms and logic by which transcription factors coordinate gene regulation requires delineation their genomic interactions at a genome-wide scale. Chromatin immunoprecipitation-sequencing (ChIP-seq) more recent techniques, including CUT&Tag, typically reveal thousands factors, but without insight into functional roles. Due to cost time considerations, optimization ChIP experimental conditions is carried out only with representative interaction sites...
ABSTRACT Development of embryonic stem cells (ESCs) into neurons requires intricate regulation transcription, splicing, and translation, but how these processes interconnect is not understood. We found that polypyrimidine tract binding protein 1 (PTBP1) alters splicing DPF2, a subunit BAF chromatin remodeling complexes. Dpf2 exon 7 inhibited by PTBP1 to produce the DPF2-S isoform early in development. During neuronal differentiation, loss allows resulting longer DPF2-L isoform. Gene...